Immune responses of liver-infiltrating lymphocytes and peripheral blood mononuclear cells to hepatitis C virus core and NS3 antigens

Background and aim: Th1/Th2 cytokine balance is thought to play an important role in antiviral immunity and pathogenesis in viral infection. Ex vivo hepatitis C virus (HCV) antigen-specific T-cell responses were investigated. Methods: Using enzyme-linked inummospot assay, HCV core and NS3 antigen-specific interferon-gamma-, interleukin-4- and interleukin-10-secreting cells were enumerated in peripheral blood mononuclear cells (PBMCs) from 30 chronic hepatitis C patients and 16 healthy controls, and in liver-infiltrating lymphocytes (LILs) from 17 of the 30 patients. Results: IFN-gamma- and IL-10-secreting cells in response to stimulation with HCV core and NS3 antigen were detectable in both PBMCs and LILs from patients with chronic hepatitis C, although frequencies of the cytokine-secreting cells were much higher in LILs than PBMCs. They were not detectable in PBMCs of healthy controls except for IL-10-secreting cells in response to HCV NS3 antigen stimulation. IL-4-secreting cells were hardly detectable in both PBMC and LIL in both the patients and the healthy controls. Frequencies of HCV NS3 antigen-specific IFN-gamma- and IL-10-secreting cells in PBMCs correlated with those in LILs (p = 0.599, p = 0.044 and p = 0.716, p = 0.004, respectively). Conclusions: These data provide further evidence of the immunomodulatory role of the CD4(+)CD25(+) regulatory T lymphocytes in chronic HCV infection. (c) 2006 Elsevier Ireland Ltd. All rights reserved.